Cord blood (CB) cells are a desirable source of stem cells for transplantation because their collection poses no donor impact and they would facilitate the creation of an ethnically diverse pool of donor cells. However, the small quantity of stem cells and the extended cytopenias associated with the use of CB cells for transplantation limit broad application to adult patients. Ex vivo protocols that enable expansion of repopulating stem cells have been developed, but require many weeks of culture, and the use of multiple manipulations and vessels that increase the risk of contamination and limit reproducibility. In order to utilize recent discoveries that low oxygen levels are favorable to stem cell expansion, Resodyn Corporation has developed the hypoxia-perfusion bioreactor (HPB), which is designed to provide controlled delivery of both oxygen and fresh medium to stem cell cultures. It is the aim of this proposal to demonstrate use of the HPB as a simple, inexpensive stem cell enrichment device, and as a stem cell expansion device that can increase the rate and quality of stem cell expansion using current state-of-the-art expansion protocols. In Phase I, feasibility will be demonstrated and the optimal oxygen levels established. In Phase II, cytokine/oxygen interactions will be explored, and a scale-up of protocols and hardware to a clinically-ready system will be accomplished. Phase III will consist of clinical trials to test the efficacy of expanded stem cells. The HPB system has significant long-term commercial potential both in the laboratory as a tool to facilitate development of stem cells protocols, and in the clinic as a component of both CB transplantation and other pre-emerging stem cell protocols of the neural, hematopoietic, and mesenchymal lineages.